3-185514381-G-A

Position:

• chr3-185514381-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000296252.9(LIPH):​c.1094+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 907,282 control chromosomes in the GnomAD database, including 82,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13438 hom., cov: 32)
  • Exomes 𝑓: 0.42 (68604 hom.)
• Consequence: LIPH ENST00000296252.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.251

Genes affected

LIPH (HGNC:18483): (lipase H) This gene encodes a membrane-bound member of the mammalian triglyceride lipase family. It catalyzes the production of 2-acyl lysophosphatidic acid (LPA), which is a lipid mediator with diverse biological properties that include platelet aggregation, smooth muscle contraction, and stimulation of cell proliferation and motility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-185514381-G-A is Benign according to our data. Variant chr3-185514381-G-A is described in ClinVar as [Benign]. Clinvar id is 1281519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPH	NM_139248.3	c.1094+29C>T		intron_variant		ENST00000296252.9	NP_640341.1
LIPH	XM_006713529.5	c.1004+29C>T		intron_variant			XP_006713592.1
LIPH	XM_011512530.4	c.965+29C>T		intron_variant			XP_011510832.1
LIPH	XM_017005852.3	c.992+29C>T		intron_variant			XP_016861341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPH	ENST00000296252.9	c.1094+29C>T		intron_variant		1	NM_139248.3	ENSP00000296252	P1
LIPH	ENST00000424591.6	c.992+29C>T		intron_variant		1		ENSP00000396384
LIPH	ENST00000435679.1	c.127+29C>T		intron_variant		5		ENSP00000390228

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63437 AN: 151894 Hom.: 13427 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.426

GnomAD3 exomes AF: 0.400 AC: 100305 AN: 250718 Hom.: 20477 AF XY: 0.398 AC XY: 53956 AN XY: 135548

Gnomad AFR exome AF: 0.401

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.296

Gnomad SAS exome AF: 0.288

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.424

GnomAD4 exome AF: 0.420 AC: 317337 AN: 755270 Hom.: 68604 Cov.: 10 AF XY: 0.415 AC XY: 167411 AN XY: 403572

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.418 AC: 63471 AN: 152012 Hom.: 13438 Cov.: 32 AF XY: 0.414 AC XY: 30741 AN XY: 74284

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.429

Alfa AF: 0.430 Hom.: 3092

Bravo AF: 0.419

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1837882; hg19: chr3-185232169; COSMIC: COSV56183247; COSMIC: COSV56183247;